Method for penetrating tissue

ABSTRACT

A tissue penetrating system has a housing member. A plurality of penetrating members are positioned in the housing member. A tissue stabilizing member is coupled to the housing. A penetrating member sensor is coupled to the plurality of penetrating members. The penetrating member sensor is configured to provide information relative to a depth of penetration of a penetrating member through a skin surface.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.12/326,698, filed Dec. 2, 2008, which is a divisional of U.S. Ser. No.11/536,720 filed Sep. 29, 2006, which is a continuation of U.S. Ser. No.10/335,212, filed Dec. 31, 2002, said Ser. No. 10/335,212 being acontinuation-in-part and of U.S. Ser. No. 10/127,395, filed Apr. 19,2002. Said Ser. No. 11/536,720 is also a continuation of U.S. Ser. No.10/237,261, filed Sep. 5, 2002, and U.S. Ser. No. 10/237,262, filed Sep.5, 2002. All applications listed above are fully incorporated herein byreference for all purposes.

BACKGROUND OF THE INVENTION

Lancing devices are known in the medical health-care products industryfor piercing the skin to produce blood for analysis. Typically, a dropof blood for this type of analysis is obtained by making a smallincision in the fingertip, creating a small wound, which generates asmall blood droplet on the surface of the skin.

Early methods of lancing included piercing or slicing the skin with aneedle or razor. Current methods utilize lancing devices that contain amultitude of spring, cam and mass actuators to drive the lancet. Theseinclude cantilever springs, diaphragms, coil springs, as well as gravityplumbs used to drive the lancet. The device may be held against the skinand mechanically triggered to ballistically launch the lancet.Unfortunately, the pain associated with each lancing event using knowntechnology discourages patients from testing. In addition to vibratorystimulation of the skin as the driver impacts the end of a launcherstop, known spring based devices have the possibility of harmonicallyoscillating against the patient tissue, causing multiple strikes due torecoil. This recoil and multiple strikes of the lancet against thepatient is one major impediment to patient compliance with a structuredglucose monitoring regime.

Another impediment to patient compliance is the lack of spontaneousblood flow generated by known lancing technology. In addition to thepain as discussed above, a patient may need more than one lancing eventto obtain a blood sample since spontaneous blood generation isunreliable using known lancing technology. Thus the pain is multipliedby the number of tries it takes to successfully generate spontaneousblood flow. Different skin thickness may yield different results interms of pain perception, blood yield and success rate of obtainingblood between different users of the lancing device. Known devicespoorly account for these skin thickness variations.

A still further impediment to improved compliance with glucosemonitoring are the many steps and hassle associated with each lancingevent. Many diabetic patients that are insulin dependent may need toself-test for blood glucose levels five to six times daily. The largenumber of steps required in traditional methods of glucose testing,ranging from lancing, to milking of blood, applying blood to the teststrip, and getting the measurements from the test strip, discouragesmany diabetic patients from testing their blood glucose levels as oftenas recommended. Older patients and those with deteriorating motor skillsencounter difficulty loading lancets into launcher devices, transferringblood onto a test strip, or inserting thin test strips into slots onglucose measurement meters. Additionally, the wound channel left on thepatient by known systems may also be of a size that discourages thosewho are active with their hands or who are worried about healing ofthose wound channels from testing their glucose levels.

SUMMARY OF THE INVENTION

Accordingly, an object of the present invention is to provide improvedtissue penetrating systems, and their methods of use.

Another object of the present invention is to provide tissue penetratingsystems, and their methods of use, that provide reduced pain whenpenetrating a target tissue.

Yet another object of the present invention is to provide tissuepenetrating systems, and their methods of use, that provide controlleddepth of penetration.

Still a further object of the present invention is to provide tissuepenetrating systems, and their methods of use, that provide controlledvelocities into and out of target tissue.

A further object of the present invention is to provide tissuepenetrating systems, and their methods of use, that provide stimulationto a target tissue.

Another object of the present invention is to provide tissue penetratingsystems, and their methods of use, that apply a pressure to a targettissue.

Yet another object of the present invention is to provide tissuepenetrating systems, and their methods of use, with penetrating membersthat remain in sterile environments prior to launch.

Still another object of the present invention is to provide tissuepenetrating systems, and their methods of use, with penetrating membersthat remain in sterile environments prior to launch, and the penetratingmembers are not used to breach the sterile environment.

A further object of the present invention is to provide improved tissuepenetrating systems, and their methods of use, that have userinterfaces.

Another object of the present invention is to provide improved tissuepenetrating systems, and their methods of use, that have humaninterfaces.

Yet another object of the present invention is to provide tissuepenetrating systems, and their methods of use, that have low volumesample chambers.

Still another object of the present invention is to provide tissuepenetrating systems, and their methods of use, that have sample chamberswith volumes that do not exceed 1 μL.

Another object of the present invention is to provide tissue penetratingsystems, and their methods of use, that have multiple penetratingmembers housed in a cartridge.

These and other objects of the present invention are achieved in atissue penetrating system with a housing member. A plurality ofpenetrating members are positioned in the housing member. A tissuestabilizing member is coupled to the housing. A penetrating membersensor is coupled to the plurality of penetrating members. Thepenetrating member sensor is configured to provide information relativeto a depth of penetration of a penetrating member through a skinsurface.

In another embodiment of the present invention, a tissue penetratingsystem includes a housing member and a plurality of penetrating members.A stimulating member is coupled to the housing member and configured toincrease blood circulation at a skin surface.

In another embodiment of the present invention, a tissue penetratingsystem includes a housing member and a plurality of penetrating members.A stimulating vibratory member is coupled to the housing member andconfigured to apply a vibratory motion to a skin surface.

In another embodiment of the present invention, a method of obtaining asample of capillary whole blood from a target tissue provides apenetrating system that includes a tissue stabilizing member. Skinstimulation is applied to a skin surface site with the tissuestabilizing member. A penetrating member is introduced through the skinsurface site to form an incision. Blood is collected from the incisionin the penetrating system.

In another embodiment of the present invention, a tissue penetratingsystem includes an electromechanical penetrating member driver. Aplurality of penetrating members each have a sharpened distal tip. Aplurality of cartridges are each associated with a penetrating memberand coupled to the penetrating member driver. Each cartridge has aplurality of seals for maintaining the distal tip of the penetratingmember in a sterile condition prior to launch. A tissue stabilizingmember is coupled to at least one of the cartridges.

In another embodiment of the present invention, a tissue penetratingsystem includes a penetrating member driver with penetrating memberposition feedback control. A plurality of penetrating members each havea sharpened distal tip. A plurality of cartridges are each associatedwith a penetrating member and coupled to the penetrating member driver.Each cartridge has a plurality of seals for maintaining the distal tipof the penetrating member in a sterile condition prior to lancing. Atissue stabilizing member is coupled to at least one of the cartridges.

In another embodiment of the present invention, a tissue penetratingsystem includes a penetrating member driver with penetrating memberposition feedback control. A plurality of penetrating members each havea sharpened distal tip. A plurality of cartridges are each associatedwith a penetrating member and coupled to the penetrating member driver.Each cartridge has a plurality of seals for maintaining the distal tipof the penetrating member in a sterile condition prior to lancing. Acartridge transport device moves each of cartridge to a position toalign the penetrating member with the penetrating member driver so thatthe penetrating member may be driven along a path into the tissue site.A tissue stabilizing member is coupled to at least one of thecartridges.

A further understanding of the nature and advantages of the inventionwill become apparent by reference to the remaining portions of thespecification and drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates an embodiment of a controllable force driver in theform of a cylindrical electric penetrating member driver using a coiledsolenoid-type configuration.

FIG. 2A illustrates a displacement over time profile of a penetratingmember driven by a harmonic spring/mass system.

FIG. 2B illustrates the velocity over time profile of a penetratingmember driver by a harmonic spring/mass system.

FIG. 2C illustrates a displacement over time profile of an embodiment ofa controllable force driver.

FIG. 2D illustrates a velocity over time profile of an embodiment of acontrollable force driver.

FIG. 3 is a diagrammatic view illustrating a controlled feed-back loop.

FIG. 4 is a perspective view of a tissue penetration device havingfeatures of the invention.

FIG. 5 is an elevation view in partial longitudinal section of thetissue penetration device of FIG. 4.

FIGS. 6A-6C show a flowchart illustrating a penetrating member controlmethod.

FIG. 7 is a diagrammatic view of a patient's finger and a penetratingmember tip moving toward the skin of the finger.

FIG. 8 is a diagrammatic view of a patient's finger and the penetratingmember tip making contact with the skin of a patient's finger.

FIG. 9 is a diagrammatic view of the penetrating member tip depressingthe skin of a patient's finger.

FIG. 10 is a diagrammatic view of the penetrating member tip furtherdepressing the skin of a patient's finger.

FIG. 11 is a diagrammatic view of the penetrating member tip penetratingthe skin of a patient's finger.

FIG. 12 is a diagrammatic view of the penetrating member tip penetratingthe skin of a patient's finger to a desired depth.

FIG. 13 is a diagrammatic view of the penetrating member tip withdrawingfrom the skin of a patient's finger.

FIGS. 14-18 illustrate a method of tissue penetration that may measureelastic recoil of the skin.

FIG. 19 is a perspective view in partial section of a tissue penetrationsampling device with a cartridge of sampling modules.

FIG. 20 is a perspective view of a sampling module cartridge with thesampling modules arranged in a ring configuration.

FIG. 21 illustrate an embodiment of a cartridge for use in samplinghaving a sampling cartridge body and a penetrating member cartridgebody.

FIG. 22A shows a device for use on a tissue site having a plurality ofpenetrating members.

FIG. 22B shows rear view of a device for use on a tissue site having aplurality of penetrating members.

FIG. 22C shows a schematic of a device for use on a tissue site with afeedback loop and optionally a damper.

FIG. 23A shows an embodiment of a device with a user interface.

FIG. 23B shows an outer view of a device with a user interface.

FIG. 24 is a cut away view of a system for sampling body fluid.

FIG. 25 is an exploded view of a cartridge for use with a system forsampling body fluid.

FIG. 26 is an exploded view of a cartridge having multiple penetratingmembers for use with a system for sampling body fluid.

FIGS. 27-28 show cartridges for use with a system for sampling bodyfluid.

FIG. 29 shows a cutaway view of another embodiment of a system forsampling body fluid.

FIG. 30 shows the density associated with a cartridge according to thepresent invention.

FIG. 31 shows a cutaway view of another embodiment of a system forsampling body fluid.

FIG. 32 is a cut away view of a cartridge according to the presentinvention.

FIGS. 33-34 show views of a body sampling system using multiplecartridges.

FIG. 35 shows an embodiment of the present invention with a tissuestabilizing member.

FIG. 36 shows a cartridge according to the present invention with atissue stabilizing member.

FIG. 37 shows a system according to the present invention with amoveable cartridge.

DESCRIPTION OF THE SPECIFIC EMBODIMENTS

The present invention provides a solution for body fluid sampling.Specifically, some embodiments of the present invention provides apenetrating member device for consistently creating a wound withspontaneous body fluid flow from a patient. The invention may be amultiple penetrating member device with an optional high density design.It may use penetrating members of smaller size than known penetratingmembers. The device may be used for multiple lancing events withouthaving to remove a disposable from the device or for the user to handlesharps. The invention may provide improved sensing capabilities. Atleast some of these and other objectives described herein will be met byembodiments of the present invention.

It is to be understood that both the foregoing general description andthe following detailed description are exemplary and explanatory onlyand are not restrictive of the invention, as claimed. It should be notedthat, as used in the specification and the appended claims, the singularforms “a”, “an” and “the” include plural referents unless the contextclearly dictates otherwise. Thus, for example, reference to “a material”may include mixtures of materials, reference to “a chamber” may includemultiple chambers, and the like. References cited herein are herebyincorporated by reference in their entirety, except to the extent thatthey conflict with teachings explicitly set forth in this specification.

In this specification and in the claims which follow, reference will bemade to a number of terms which shall be defined to have the followingmeanings:

“Optional” or “optionally” means that the subsequently describedcircumstance may or may not occur, so that the description includesinstances where the circumstance occurs and instances where it does not.For example, if a device optionally contains a feature for analyzing ablood sample, this means that the analysis feature may or may not bepresent, and, thus, the description includes structures wherein a devicepossesses the analysis feature and structures wherein the analysisfeature is not present.

“Analyte detecting member” refers to any use, singly or in combination,of chemical test reagents and methods, electrical test circuits andmethods, physical test components and methods, optical test componentsand methods, and biological test reagents and methods to yieldinformation about a blood sample. Such methods are well known in the artand may be based on teachings of, e.g. Tietz Textbook of ClinicalChemistry, 3d Ed., Sec. V, pp. 776-78 (Burtis & Ashwood, Eds., W.B.Saunders Company, Philadelphia, 1999); U.S. Pat. No. 5,997,817 toChrismore et al. (Dec. 7, 1999); U.S. Pat. No. 5,059,394 to Phillips etal. (Oct. 22, 1991); U.S. Pat. No. 5,001,054 to Wagner et al. (Mar. 19,1991); and U.S. Pat. No. 4,392,933 to Nakamura et al. (Jul. 12, 1983),the teachings of which are hereby incorporated by reference, as well asothers. Analyte detecting member may include tests in the sample testchamber that test electrochemical properties of the blood, or they mayinclude optical means for sensing optical properties of the blood (e.g.oxygen saturation level), or they may include biochemical reagents (e.g.antibodies) to sense properties (e.g. presence of antigens) of theblood. The analyte detecting member may comprise biosensing or reagentmaterial that will react with an analyte in blood (e.g. glucose) orother body fluid so that an appropriate signal correlating with thepresence of the analyte is generated and can be read by the readerapparatus. By way of example and not limitation, analyte detectingmember may “associated with”, “mounted within”, or “coupled to” achamber or other structure when the analyte detecting memberparticipates in the function of providing an appropriate signal aboutthe blood sample to the reader device. Analyte detecting member may alsoinclude nanowire analyte detecting members as described herein. Analytedetecting member may use potentiometric, coulometric, or other methoduseful for detection of analyte levels.

The present invention may be used with a variety of differentpenetrating member drivers. It is contemplated that these penetratingmember drivers may be spring based, solenoid based, magnetic driverbased, nanomuscle based, or based on any other mechanism useful inmoving a penetrating member along a path into tissue. It should be notedthat the present invention is not limited by the type of driver usedwith the penetrating member feed mechanism. One suitable penetratingmember driver for use with the present invention is shown in FIG. 1.This is an embodiment of a solenoid type electromagnetic driver that iscapable of driving an iron core or slug mounted to the penetratingmember assembly using a direct current (DC) power supply. Theelectromagnetic driver includes a driver coil pack that is divided intothree separate coils along the path of the penetrating member, two endcoils and a middle coil. Direct current is alternated to the coils toadvance and retract the penetrating member. Although the driver coilpack is shown with three coils, any suitable number of coils may beused, for example, 4, 5, 6, 7 or more coils may be used.

Referring to the embodiment of FIG. 1, the stationary iron housing 10may contain the driver coil pack with a first coil 12 flanked by ironspacers 14 which concentrate the magnetic flux at the inner diametercreating magnetic poles. The inner insulating housing 16 isolates thepenetrating member 18 and iron core 20 from the coils and provides asmooth, low friction guide surface. The penetrating member guide 22further centers the penetrating member 18 and iron core 20. Thepenetrating member 18 is protracted and retracted by alternating thecurrent between the first coil 12, the middle coil, and the third coilto attract the iron core 20. Reversing the coil sequence and attractingthe core and penetrating member back into the housing retracts thepenetrating member. The penetrating member guide 22 also serves as astop for the iron core 20 mounted to the penetrating member 18.

As discussed above, tissue penetration devices which employ spring orcam driving methods have a symmetrical or nearly symmetrical actuationdisplacement and velocity profiles on the advancement and retraction ofthe penetrating member as shown in FIGS. 2 and 3. In most of theavailable lancet devices, once the launch is initiated, the storedenergy determines the velocity profile until the energy is dissipated.Controlling impact, retraction velocity, and dwell time of thepenetrating member within the tissue can be useful in order to achieve ahigh success rate while accommodating variations in skin properties andminimize pain. Advantages can be achieved by taking into account of thefact that tissue dwell time is related to the amount of skin deformationas the penetrating member tries to puncture the surface of the skin andvariance in skin deformation from patient to patient based on skinhydration.

In this embodiment, the ability to control velocity and depth ofpenetration may be achieved by use of a controllable force driver wherefeedback is an integral part of driver control. Such drivers can controleither metal or polymeric penetrating members or any other type oftissue penetration element. The dynamic control of such a driver isillustrated in FIG. 2C which illustrates an embodiment of a controlleddisplacement profile and FIG. 2D which illustrates an embodiment of athe controlled velocity profile. These are compared to FIGS. 2A and 2B,which illustrate embodiments of displacement and velocity profiles,respectively, of a harmonic spring/mass powered driver. Reduced pain canbe achieved by using impact velocities of greater than about 2 m/s entryof a tissue penetrating element, such as a lancet, into tissue. Othersuitable embodiments of the penetrating member driver are described incommonly assigned, copending U.S. patent application Ser. No.10/127,395, filed Apr. 19, 2002 and previously incorporated herein.

FIG. 3 illustrates the operation of a feedback loop using a processor60. The processor 60 stores profiles 62 in non-volatile memory. A userinputs information 64 about the desired circumstances or parameters fora lancing event. The processor 60 selects a driver profile 62 from a setof alternative driver profiles that have been preprogrammed in theprocessor 60 based on typical or desired tissue penetration deviceperformance determined through testing at the factory or as programmedin by the operator. The processor 60 may customize by either scaling ormodifying the profile based on additional user input information 64.Once the processor has chosen and customized the profile, the processor60 is ready to modulate the power from the power supply 66 to thepenetrating member driver 68 through an amplifier 70. The processor 60may measure the location of the penetrating member 72 using a positionsensing mechanism 74 through an analog to digital converter 76 linearencoder or other such transducer. Examples of position sensingmechanisms have been described in the embodiments above and may be foundin the specification for commonly assigned, copending U.S. patentapplication Ser. No. 10/127,395, filed Apr. 19, 2002 and previouslyincorporated herein. The processor 60 calculates the movement of thepenetrating member by comparing the actual profile of the penetratingmember to the predetermined profile. The processor 60 modulates thepower to the penetrating member driver 68 through a signal generator 78,which may control the amplifier 70 so that the actual velocity profileof the penetrating member does not exceed the predetermined profile bymore than a preset error limit. The error limit is the accuracy in thecontrol of the penetrating member.

After the lancing event, the processor 60 can allow the user to rank theresults of the lancing event. The processor 60 stores these results andconstructs a database 80 for the individual user. Using the database 79,the processor 60 calculates the profile traits such as degree ofpainlessness, success rate, and blood volume for various profiles 62depending on user input information 64 to optimize the profile to theindividual user for subsequent lancing cycles. These profile traitsdepend on the characteristic phases of penetrating member advancementand retraction. The processor 60 uses these calculations to optimizeprofiles 62 for each user. In addition to user input information 64, aninternal clock allows storage in the database 79 of information such asthe time of day to generate a time stamp for the lancing event and thetime between lancing events to anticipate the user's diurnal needs. Thedatabase stores information and statistics for each user and eachprofile that particular user uses.

In addition to varying the profiles, the processor 60 can be used tocalculate the appropriate penetrating member diameter and geometrysuitable to realize the blood volume required by the user. For example,if the user requires about 1-5 microliter volume of blood, the processor60 may select a 200 micron diameter penetrating member to achieve theseresults. For each class of lancet, both diameter and lancet tipgeometry, is stored in the processor 60 to correspond with upper andlower limits of attainable blood volume based on the predetermineddisplacement and velocity profiles.

The lancing device is capable of prompting the user for information atthe beginning and the end of the lancing event to more adequately suitthe user. The goal is to either change to a different profile or modifyan existing profile. Once the profile is set, the force driving thepenetrating member is varied during advancement and retraction to followthe profile. The method of lancing using the lancing device comprisesselecting a profile, lancing according to the selected profile,determining lancing profile traits for each characteristic phase of thelancing cycle, and optimizing profile traits for subsequent lancingevents.

FIG. 4 illustrates an embodiment of a tissue penetration device, morespecifically, a lancing device 80 that includes a controllable driver179 coupled to a tissue penetration element. The lancing device 80 has aproximal end 81 and a distal end 82. At the distal end 82 is the tissuepenetration element in the form of a penetrating member 83, which iscoupled to an elongate coupler shaft 84 by a drive coupler 85. Theelongate coupler shaft 84 has a proximal end 86 and a distal end 87. Adriver coil pack 88 is disposed about the elongate coupler shaft 84proximal of the penetrating member 83. A position sensor 91 is disposedabout a proximal portion 92 of the elongate coupler shaft 84 and anelectrical conductor 94 electrically couples a processor 93 to theposition sensor 91. The elongate coupler shaft 84 driven by the drivercoil pack 88 controlled by the position sensor 91 and processor 93 formthe controllable driver, specifically, a controllable electromagneticdriver.

Referring to FIG. 5, the lancing device 80 can be seen in more detail,in partial longitudinal section. The penetrating member 83 has aproximal end 95 and a distal end 96 with a sharpened point at the distalend 96 of the penetrating member 83 and a drive head 98 disposed at theproximal end 95 of the penetrating member 83. A penetrating member shaft201 is disposed between the drive head 98 and the sharpened point 97.The penetrating member shaft 201 may be comprised of stainless steel, orany other suitable material or alloy and have a transverse dimension ofabout 0.1 to about 0.4 mm. The penetrating member shaft may have alength of about 3 mm to about 50 mm, specifically, about 15 mm to about20 mm. The drive head 98 of the penetrating member 83 is an enlargedportion having a transverse dimension greater than a transversedimension of the penetrating member shaft 201 distal of the drive head98. This configuration allows the drive head 98 to be mechanicallycaptured by the drive coupler 85. The drive head 98 may have atransverse dimension of about 0.5 to about 2 mm.

A magnetic member 102 is secured to the elongate coupler shaft 84proximal of the drive coupler 85 on a distal portion 203 of the elongatecoupler shaft 84. The magnetic member 102 is a substantially cylindricalpiece of magnetic material having an axial lumen 204 extending thelength of the magnetic member 102. The magnetic member 102 has an outertransverse dimension that allows the magnetic member 102 to slide easilywithin an axial lumen 105 of a low friction, possibly lubricious,polymer guide tube 105′ disposed within the driver coil pack 88. Themagnetic member 102 may have an outer transverse dimension of about 1.0to about 5.0 mm, specifically, about 2.3 to about 2.5 mm. The magneticmember 102 may have a length of about 3.0 to about 5.0 mm, specifically,about 4.7 to about 4.9 mm. The magnetic member 102 can be made from avariety of magnetic materials including ferrous metals such as ferroussteel, iron, ferrite, or the like. The magnetic member 102 may besecured to the distal portion 203 of the elongate coupler shaft 84 by avariety of methods including adhesive or epoxy bonding, welding,crimping or any other suitable method.

Proximal of the magnetic member 102, an optical encoder flag 206 issecured to the elongate coupler shaft 84. The optical encoder flag 206is configured to move within a slot 107 in the position sensor 91. Theslot 107 of the position sensor 91 is formed between a first bodyportion 108 and a second body portion 109 of the position sensor 91. Theslot 107 may have separation width of about 1.5 to about 2.0 mm. Theoptical encoder flag 206 can have a length of about 14 to about 18 mm, awidth of about 3 to about 5 mm and a thickness of about 0.04 to about0.06 mm.

The optical encoder flag 206 interacts with various optical beamsgenerated by LEDs disposed on or in the position sensor body portions108 and 109 in a predetermined manner. The interaction of the opticalbeams generated by the LEDs of the position sensor 91 generates a signalthat indicates the longitudinal position of the optical flag 206relative to the position sensor 91 with a substantially high degree ofresolution. The resolution of the position sensor 91 may be about 200 toabout 400 cycles per inch, specifically, about 350 to about 370 cyclesper inch. The position sensor 91 may have a speed response time(position/time resolution) of 0 to about 120,000 Hz, where one dark andlight stripe of the flag constitutes one Hertz, or cycle per second. Theposition of the optical encoder flag 206 relative to the magnetic member102, driver coil pack 88 and position sensor 91 is such that the opticalencoder 91 can provide precise positional information about thepenetrating member 83 over the entire length of the penetrating member'spower stroke.

An optical encoder that is suitable for the position sensor 91 is alinear optical incremental encoder, model HEDS 9200, manufactured byAgilent Technologies. The model HEDS 9200 may have a length of about 20to about 30 mm, a width of about 8 to about 12 mm, and a height of about9 to about 11 mm. Although the position sensor 91 illustrated is alinear optical incremental encoder, other suitable position sensorembodiments could be used, provided they posses the requisite positionalresolution and time response. The HEDS 9200 is a two channel devicewhere the channels are 90 degrees out of phase with each other. Thisresults in a resolution of four times the basic cycle of the flag. Thesequadrature outputs make it possible for the processor to determine thedirection of penetrating member travel. Other suitable position sensorsinclude capacitive encoders, analog reflective sensors, such as thereflective position sensor discussed above, and the like.

A coupler shaft guide 111 is disposed towards the proximal end 81 of thelancing device 80. The guide 111 has a guide lumen 112 disposed in theguide 111 to slidingly accept the proximal portion 92 of the elongatecoupler shaft 84. The guide 111 keeps the elongate coupler shaft 84centered horizontally and vertically in the slot 102 of the opticalencoder 91.

The driver coil pack 88, position sensor 91 and coupler shaft guide 111are all secured to a base 113. The base 113 is longitudinallycoextensive with the driver coil pack 88, position sensor 91 and couplershaft guide 111. The base 113 can take the form of a rectangular pieceof metal or polymer, or may be a more elaborate housing with recesses,which are configured to accept the various components of the lancingdevice 80.

As discussed above, the magnetic member 102 is configured to slidewithin an axial lumen 105 of the driver coil pack 88. The driver coilpack 88 includes a most distal first coil 114, a second coil 115, whichis axially disposed between the first coil 114 and a third coil 116, anda proximal-most fourth coil 117. Each of the first coil 114, second coil115, third coil 116 and fourth coil 117 has an axial lumen. The axiallumens of the first through fourth coils are configured to be coaxialwith the axial lumens of the other coils and together form the axiallumen 105 of the driver coil pack 88 as a whole. Axially adjacent eachof the coils 114-117 is a magnetic disk or washer 118 that augmentscompletion of the magnetic circuit of the coils 114-117 during a lancingcycle of the device 80. The magnetic washers 118 of the embodiment ofFIG. 5 are made of ferrous steel but could be made of any other suitablemagnetic material, such as iron or ferrite. The outer shell 89 of thedriver coil pack 88 is also made of iron or steel to complete themagnetic path around the coils and between the washers 118. The magneticwashers 118 have an outer diameter commensurate with an outer diameterof the driver coil pack 88 of about 4.0 to about 8.0 mm. The magneticwashers 118 have an axial thickness of about 0.05, to about 0.4 mm,specifically, about 0.15 to about 0.25 mm.

Wrapping or winding an elongate electrical conductor 121 about an axiallumen until a sufficient number of windings have been achieved forms thecoils 114-117. The elongate electrical conductor 121 is generally aninsulated solid copper wire with a small outer transverse dimension ofabout 0.06 mm to about 0.88 mm, specifically, about 0.3 mm to about 0.5mm. In one embodiment, 32 gauge copper wire is used for the coils114-117. The number of windings for each of the coils 114-117 of thedriver pack 88 may vary with the size of the coil, but for someembodiments each coil 114-117 may have about 30 to about 80 turns,specifically, about 50 to about 60 turns. Each coil 114-117 can have anaxial length of about 1.0 to about 3.0 mm, specifically, about 1.8 toabout 2.0 mm. Each coil 114-117 can have an outer transverse dimensionor diameter of about 4.0, to about 2.0 mm, specifically, about 9.0 toabout 12.0 mm. The axial lumen 105 can have a transverse dimension ofabout 1.0 to about 3.0 mm.

It may be advantageous in some driver coil 88 embodiments to replace oneor more of the coils with permanent magnets, which produce a magneticfield similar to that of the coils when the coils are activated. Inparticular, it may be desirable in some embodiments to replace thesecond coil 115, the third coil 116 or both with permanent magnets. Inaddition, it may be advantageous to position a permanent magnet at ornear the proximal end of the coil driver pack in order to provide fixedmagnet zeroing function for the magnetic member (Adams magnetic Products23A0002 flexible magnet material (800) 747-7543).

A permanent bar magnet 119 disposed on the proximal end of the drivercoil pack 88. As shown in FIG. 5, the bar magnet 119 is arranged so asto have one end disposed adjacent the travel path of the magnetic member102 and has a polarity configured so as to attract the magnetic member102 in a centered position with respect to the bar magnet 119. Note thatthe polymer guide tube 105′ can be configured to extend proximally toinsulate the inward radial surface of the bar magnet 119 from an outersurface of the magnetic member 102. This arrangement allows the magneticmember 119 and thus the elongate coupler shaft 84 to be attracted to andheld in a zero point or rest position without the consumption ofelectrical energy from the power supply 125.

Having a fixed zero or start point for the elongate coupler shaft 84 andpenetrating member 83 may be useful to properly controlling the depth ofpenetration of the penetrating member 83 as well as other lancingparameters. This can be because some methods of depth penetrationcontrol for a controllable driver measure the acceleration anddisplacement of the elongate coupler shaft 84 and penetrating member 83from a known start position. If the distance of the penetrating membertip 96 from the target tissue is known, acceleration and displacement ofthe penetrating member is known and the start position of thepenetrating member is know, the time and position of tissue contact anddepth of penetration can be determined by the processor 93.

Any number of configurations for a magnetic bar 119 can be used for thepurposes discussed above. In particular, a second permanent bar magnet(not shown) could be added to the proximal end of the driver coil pack88 with the magnetic fields of the two bar magnets configured tocomplement each other. In addition, a disc magnet could be used asillustrated in FIG. 23(a). The disc magnet is shown disposed at theproximal end of the driver coiled pack 88 with a polymer non-magneticdisc disposed between the proximal-most coil 117 and disc magnet andpositions disc magnet away from the proximal end of the proximal-mostcoil 117. The polymer non-magnetic disc spacer is used so that themagnetic member 102 can be centered in a zero or start position slightlyproximal of the proximal-most coil 117 of the driver coil pack 88. Thisallows the magnetic member to be attracted by the proximal-most coil 117at the initiation of the lancing cycle instead of being passive in theforward drive portion of the lancing cycle.

An inner lumen of the polymer non-magnetic disc can be configured toallow the magnetic member 102 to pass axially there through while aninner lumen of the disc magnet can be configured to allow the elongatecoupler shaft 84 to pass through but not large enough for the magneticmember 102 to pass through. This results in the magnetic member 102being attracted to the disc magnet and coming to rest with the proximalsurface of the magnetic member 102 against a distal surface of the discmagnet. This arrangement provides for a positive and repeatable stop forthe magnetic member, and hence the penetrating member.

Typically, when the electrical current in the coils 114-117 of thedriver coil pack 88 is off, a magnetic member 102 made of soft iron isattracted to the bar magnet 119 or the disc magnet. The magnetic fieldof the driver coil pack 88 and the bar magnet 119 or the disc magnet, orany other suitable magnet, can be configured such that when theelectrical current in the coils 114-117 is turned on, the leakagemagnetic field from the coils 114-117 has the same polarity as the barmagnet 119 or the disc magnet. This results in a magnetic force thatrepels the magnetic member 102 from the bar magnet 119 or disc magnetand attracts the magnetic member 102 to the activated coils 114-117. Forthis configuration, the bar magnet 119 or disc magnet thus act tofacilitate acceleration of the magnetic member 102 as opposed to workingagainst the acceleration.

Electrical conductors 122 couple the driver coil pack 88 with theprocessor 93 which can be configured or programmed to control thecurrent flow in the coils 114-117 of the driver coil pack 88 based onposition feedback from the position sensor 91, which is coupled to theprocessor 93 by electrical conductors 94. A power source 125 iselectrically coupled to the processor 93 and provides electrical powerto operate the processor 93 and power the coil driver pack 88. The powersource 125 may be one or more batteries that provide direct currentpower to the 93 processor.

Referring to FIGS. 29A-29C, a flow diagram is shown that describes theoperations performed by the processor 93 in controlling the penetratingmember 83 of the lancing device 80 discussed above during an operatingcycle. FIGS. 30-36 illustrate the interaction of the penetrating member83 and skin 133 of the patient's finger 134 during an operation cycle ofthe penetrating member device 83. The processor 93 operates undercontrol of programming steps that are stored in an associated memory.When the programming steps are executed, the processor 93 performsoperations as described herein. Thus, the programming steps implementthe functionality of the operations described with respect to the flowdiagram of FIG. 29. The processor 93 can receive the programming stepsfrom a program product stored in recordable media, including a directaccess program product storage device such as a hard drive or flash ROM,a removable program product storage device such as a floppy disk, or inany other manner known to those of skill in the art. The processor 93can also download the programming steps through a network connection orserial connection.

In the first operation, represented by the flow diagram box numbered 245in FIG. 6A, the processor 93 initializes values that it stores in memoryrelating to control of the penetrating member, such as variables that ituses to keep track of the controllable driver 179 during movement. Forexample, the processor may set a clock value to zero and a penetratingmember position value to zero or to some other initial value. Theprocessor 93 may also cause power to be removed from the coil pack 88for a period of time, such as for about 10 ms, to allow any residualflux to dissipate from the coils.

In the initialization operation, the processor 93 also causes thepenetrating member to assume an initial stationary position. When in theinitial stationary position, the penetrating member 83 is typicallyfully retracted such that the magnetic member 102 is positionedsubstantially adjacent the fourth coil 117 of the driver coil pack 88,shown in FIG. 5 above. The processor 93 can move the penetrating member83 to the initial stationary position by pulsing an electrical currentto the fourth coil 117 to thereby attract the magnetic member 102 on thepenetrating member 83 to the fourth coil 117. Alternatively, themagnetic member can be positioned in the initial stationary position byvirtue of a permanent magnet, such as bar magnet 119, the disc magnet orany other suitable magnet as discussed above with regard to the tissuepenetration device illustrated in FIGS. 20 and 21.

In the next operation, represented by the flow diagram box numbered 247,the processor 93 energizes one or more of the coils in the coil pack 88.This should cause the penetrating member 83 to begin to move (i.e.,achieve a non-zero speed) toward the skin target 133. The processor 93then determines whether or not the penetrating member is indeed moving.The processor 93 can determine whether the penetrating member 83 ismoving by monitoring the position of the penetrating member 83 todetermine whether the position changes over time. The processor 93 canmonitor the position of the penetrating member 83 by keeping track ofthe position of the optical encoder flag 106 secured to the elongatecoupler shaft 84 wherein the encoder 91 produces a signal coupled to theprocessor 93 that indicates the spatial position of the penetratingmember 83.

If the processor 93 determines (via timeout without motion events) thatthe penetrating member 83 is not moving (a “No” result from the decisionbox), then the process proceeds to the operation, where the processordeems that an error condition is present. This means that some error inthe system is causing the penetrating member 83 not to move. The errormay be mechanical, electrical, or software related. For example, thepenetrating member 83 may be stuck in the stationary position becausesomething is impeding its movement.

If the processor 93 determines that the penetrating member 83 is indeedmoving (a “Yes” result from the decision box numbered 249), then theprocess proceeds to the operation represented by the flow diagram boxnumbered 257. In this operation, the processor 93 causes the penetratingmember 83 to continue to accelerate and launch toward the skin target133, as indicated by the arrow 135 in FIG. 7. The processor 93 canachieve acceleration of the penetrating member 83 by sending anelectrical current to an appropriate coil 114-117 such that the coil114-117 exerts an attractive magnetic launching force on the magneticmember 102 and causes the magnetic member 102 and the penetrating member83 coupled thereto to move in a desired direction. For example, theprocessor 93 can cause an electrical current to be sent to the thirdcoil 116 so that the third coil 116 attracts the magnetic member 102 andcauses the magnetic member 102 to move from a position adjacent thefourth coil 117 toward the third coil 116. The processor preferablydetermines which coil 114-117 should be used to attract the magneticmember 102 based on the position of the magnetic member 102 relative tothe coils 114-117. In this manner, the processor 93 provides acontrolled force to the penetrating member that controls the movement ofthe penetrating member.

During this operation, the processor 93 periodically or continuallymonitors the position and/or velocity of the penetrating member 83. Inkeeping track of the velocity and position of the penetrating member 83as the penetrating member 83 moves towards the patient's skin 133 orother tissue, the processor 93 also monitors and adjusts the electricalcurrent to the coils 114-117. In some embodiments, the processor 93applies current to an appropriate coil 114-117 such that the penetratingmember 83 continues to move according to a desired direction andacceleration. In the instant case, the processor 93 applies current tothe appropriate coil 114-117 that will cause the penetrating member 83to continue to move in the direction of the patient's skin 133 or othertissue to be penetrated.

The processor 93 may successively transition the current between coils114-117 so that as the magnetic member 102 moves past a particular coil114-117, the processor 93 then shuts off current to that coil 114-117and then applies current to another coil 114-117 that will attract themagnetic member 102 and cause the magnetic member 102 to continue tomove in the desired direction. In transitioning current between thecoils 114-117, the processor 93 can take into account various factors,including the speed of the penetrating member 83, the position of thepenetrating member 83 relative to the coils 114-117, the number of coils114-117, and the level of current to be applied to the coils 114-117 toachieve a desired speed or acceleration.

In the next operation, the processor 93 determines whether the cuttingor distal end tip 96 of the penetrating member 83 has contacted thepatient's skin 133, as shown in FIG. 8 and as represented in FIG. 6B.The processor 93 may determine whether the penetrating member 83 hasmade contact with the target tissue 133 by a variety of methods,including some that rely on parameters which are measured prior toinitiation of a lancing cycle and other methods that are adaptable touse during a lancing cycle without any predetermined parameters.

In one embodiment, the processor 93 determines that the skin has beencontacted when the end tip 96 of the penetrating member 83 has moved apredetermined distance with respect to its initial position. If thedistance from the tip 261 of the penetrating member 83 to the targettissue 133 is known prior to initiation of penetrating member 83movement, the initial position of the penetrating member 83 is fixed andknown, and the movement and position of the penetrating member 83 can beaccurately measured during a lancing cycle, then the position and timeof penetrating member contact can be determined.

This method requires an accurate measurement of the distance between thepenetrating member tip 96 and the patient's skin 133 when thepenetrating member 83 is in the zero time or initial position. This canbe accomplished in a number of ways. One way is to control all of themechanical parameters that influence the distance from the penetratingmember tip 96 to the patient's tissue or a surface of the lancing device80 that will contact the patient's skin 133. This could include thestart position of the magnetic member 102, magnetic path tolerance,magnetic member 102 dimensions, driver coil pack 88 location within thelancing device 80 as a whole, length of the elongate coupling shaft 84,placement of the magnetic member 102 on the elongate coupling shaft 84,length of the penetrating member 83 etc.

If all these parameters, as well as others can be suitably controlled inmanufacturing with a tolerance stack-up that is acceptable, then thedistance from the penetrating member tip 96 to the target tissue 133 canbe determined at the time of manufacture of the lancing device 80. Thedistance could then be programmed into the memory of the processor 93.If an adjustable feature is added to the lancing device 80, such as anadjustable length elongate coupling shaft 84, this can accommodatevariations in all of the parameters noted above, except length of thepenetrating member 83. An electronic alternative to this mechanicalapproach would be to calibrate a stored memory contact point into thememory of the processor 93 during manufacture based on the mechanicalparameters described above.

In another embodiment, moving the penetrating member tip 96 to thetarget tissue 133 very slowly and gently touching the skin 133 prior toactuation can accomplish the distance from the penetrating member tip 96to the tissue 133. The position sensor can accurately measure thedistance from the initialization point to the point of contact, wherethe resistance to advancement of the penetrating member 83 stops thepenetrating member movement. The penetrating member 83 is then retractedto the initialization point having measured the distance to the targettissue 133 without creating any discomfort to the user.

In another embodiment, the processor 93 may use software to determinewhether the penetrating member 83 has made contact with the patient'sskin 133 by measuring for a sudden reduction in velocity of thepenetrating member 83 due to friction or resistance imposed on thepenetrating member 83 by the patient's skin 133. The optical encoder 91measures displacement of the penetrating member 83. The position outputdata provides input to the interrupt input of the processor 93. Theprocessor 93 also has a timer capable of measuring the time betweeninterrupts. The distance between interrupts is known for the opticalencoder 91, so the velocity of the penetrating member 83 can becalculated by dividing the distance between interrupts by the timebetween the interrupts.

This method requires that velocity losses to the penetrating member 83and elongate coupler 84 assembly due to friction are known to anacceptable level so that these velocity losses and resultingdeceleration can be accounted for when establishing a decelerationthreshold above which contact between penetrating member tip 96 andtarget tissue 133 will be presumed. This same concept can be implementedin many ways. For example, rather than monitoring the velocity of thepenetrating member 83, if the processor 93 is controlling thepenetrating member driver in order to maintain a fixed velocity, thepower to the driver 88 could be monitored. If an amount of power above apredetermined threshold is required in order to maintain a constantvelocity, then contact between the tip of the penetrating member 96 andthe skin 133 could be presumed.

In yet another embodiment, the processor 93 determines skin 133 contactby the penetrating member 83 by detection of an acoustic signal producedby the tip 96 of the penetrating member 83 as it strikes the patient'sskin 133. Detection of the acoustic signal can be measured by anacoustic detector 136 placed in contact with the patient's skin 133adjacent a penetrating member penetration site 137, as shown in FIG. 8.Suitable acoustic detectors 136 include piezo electric transducers,microphones and the like. The acoustic detector 136 transmits anelectrical signal generated by the acoustic signal to the processor 93via electrical conductors 138. In another embodiment, contact of thepenetrating member 83 with the patient's skin 133 can be determined bymeasurement of electrical continuity in a circuit that includes thepenetrating member 83, the patient's finger 134 and an electricalcontact pad 240 that is disposed on the patient's skin 133 adjacent thecontact site 137 of the penetrating member 83, as shown in FIG. 8. Inthis embodiment, as soon as the penetrating member 83 contacts thepatient's skin 133, the circuit 139 is completed and current flowsthrough the circuit 139. Completion of the circuit 139 can then bedetected by the processor 93 to confirm skin 133 contact by thepenetrating member 83.

If the penetrating member 83 has not contacted the target skin 133, thenthe process proceeds to a timeout operation, as represented in FIG. 6B.In the timeout operation, the processor 93 waits a predetermined timeperiod. If the timeout period has not yet elapsed, then the processorcontinues to monitor whether the penetrating member has contacted thetarget skin 133. The processor 93 preferably continues to monitor theposition and speed of the penetrating member 83, as well as theelectrical current to the appropriate coil 114-117 to maintain thedesired penetrating member 83 movement.

If the timeout period elapses without the penetrating member 83contacting the skin, then it is deemed that the penetrating member 83will not contact the skin and the process proceeds to a withdraw phase,where the penetrating member is withdrawn away from the skin 133, asdiscussed more fully below. The penetrating member 83 may not havecontacted the target skin 133 for a variety of reasons, such as if thepatient removed the skin 133 from the lancing device or if somethingobstructed the penetrating member 83 prior to it contacting the skin.

The processor 93 may also proceed to the withdraw phase prior to skincontact for other reasons. For example, at some point after initiationof movement of the penetrating member 83, the processor 93 may determinethat the forward acceleration of the penetrating member 83 towards thepatient's skin 133 should be stopped or that current to all coils114-117 should be shut down. This can occur, for example, if it isdetermined that the penetrating member 83 has achieved sufficientforward velocity, but has not yet contacted the skin 133. In oneembodiment, the average penetration velocity of the penetrating member83 from the point of contact with the skin to the point of maximumpenetration may be about 2.0 to about 10.0 m/s, specifically, about 3.8to about 4.2 m/s. In another embodiment, the average penetrationvelocity of the penetrating member may be from about 2 to about 8 metersper second, specifically, about 2 to about 4 m/s.

The processor 93 can also proceed to the withdraw phase if it isdetermined that the penetrating member 83 has fully extended to the endof the power stroke of the operation cycle of lancing procedure. Inother words, the process may proceed to withdraw phase when an axialcenter 141 of the magnetic member 102 has moved distal of an axialcenter 142 of the first coil 114 as show in FIG. 5. In this situation,any continued power to any of the coils 114-117 of the driver coil pack88 serves to decelerate the magnetic member 102 and thus the penetratingmember 83. In this regard, the processor 93 considers the length of thepenetrating member 83 (which can be stored in memory) the position ofthe penetrating member 83 relative to the magnetic member 102, as wellas the distance that the penetrating member 83 has traveled.

With reference again to FIG. 6B, if the processor 93 determines that thepenetrating member 83 has contacted the skin 133, then the processor 93can adjust the speed of the penetrating member 83 or the power deliveredto the penetrating member 83 for skin penetration to overcome anyfrictional forces on the penetrating member 83 in order to maintain adesired penetration velocity of the penetrating member.

As the velocity of the penetrating member 83 is maintained after contactwith the skin 133, the distal tip 96 of the penetrating member 83 willfirst begin to depress or tent the contacted skin 137 and the skin 133adjacent the penetrating member 83 to form a tented portion 243 as shownin FIG. 9 and further shown in FIG. 10. As the penetrating member 83continues to move in a distal direction or be driven in a distaldirection against the patient's skin 133, the penetrating member 83 willeventually begin to penetrate the skin 133, as shown in FIG. 11. Oncepenetration of the skin 133 begins, the static force at the distal tip96 of the penetrating member 83 from the skin 133 will become a dynamiccutting force, which is generally less than the static tip force. As aresult in the reduction of force on the distal tip 96 of the penetratingmember 83 upon initiation of cutting, the tented portion 243 of the skin133 adjacent the distal tip 96 of the penetrating member 83 which hadbeen depressed as shown in FIGS. 32 and 24 will spring back as shown inFIG. 11.

In the next operation, represented by the decision box numbered 171 inFIG. 6B, the processor 93 determines whether the distal end 96 of thepenetrating member 83 has reached a brake depth. The brake depth is theskin penetration depth for which the processor 93 determines thatdeceleration of the penetrating member 83 is to be initiated in order toachieve a desired final penetration depth 144 of the penetrating member83 as show in FIG. 12. The brake depth may be pre-determined andprogrammed into the processor's memory, or the processor 93 maydynamically determine the brake depth during the actuation. The amountof penetration of the penetrating member 83 in the skin 133 of thepatient may be measured during the operation cycle of the penetratingmember device 80. In addition, as discussed above, the penetration depthsuitable for successfully obtaining a useable sample can depend on theamount of tenting of the skin 133 during the lancing cycle. The amountof tenting of the patient's skin 133 can in turn depend on the tissuecharacteristics of the patient such as elasticity, hydration etc. Amethod for determining these characteristics is discussed below withregard to skin 133 tenting measurements during the lancing cycle andillustrated in FIGS. 37-41.

Penetration measurement can be carried out by a variety of methods thatare not dependent on measurement of tenting of the patient's skin. Inone embodiment, the penetration depth of the penetrating member 83 inthe patient's skin 133 is measured by monitoring the amount ofcapacitance between the penetrating member 83 and the patient's skin133. In this embodiment, a circuit includes the penetrating member 83,the patient's finger 134, the processor 93 and electrical conductorsconnecting these elements. As the penetrating member 83 penetrates thepatient's skin 133, the greater the amount of penetration, the greaterthe surface contact area between the penetrating member 83 and thepatient's skin 133. As the contact area increases, so does thecapacitance between the skin 133 and the penetrating member 83. Theincreased capacitance can be easily measured by the processor 93 usingmethods known in the art and penetration depth can then be correlated tothe amount of capacitance. The same method can be used by measuring theelectrical resistance between the penetrating member 83 and thepatient's skin.

If the brake depth has not yet been reached, then a “No” results fromthe decision box 171 and the process proceeds to the timeout operationrepresented by the flow diagram box numbered 173. In the timeoutoperation, the processor 93 waits a predetermined time period. If thetimeout period has not yet elapsed (a “No” outcome from the decision box173), then the processor continues to monitor whether the brake depthhas been reached. If the timeout period elapses without the penetratingmember 83 achieving the brake depth (a “Yes” output from the decisionbox 173), then the processor 93 deems that the penetrating member 83will not reach the brake depth and the process proceeds to the withdrawphase, which is discussed more fully below. This may occur, for example,if the penetrating member 83 is stuck at a certain depth.

With reference again to the decision box numbered 171 in FIG. 6B, if thepenetrating member does reach the brake depth (a “Yes” result), then theprocess proceeds to the operation represented by the flow diagram boxnumbered 275. In this operation, the processor 93 causes a braking forceto be applied to the penetrating member to thereby reduce the speed ofthe penetrating member 83 to achieve a desired amount of final skinpenetration depth 144, as shown in FIG. 26. Note that FIGS. 32 and 33illustrate the penetrating member making contact with the patient's skinand deforming or depressing the skin prior to any substantialpenetration of the skin. The speed of the penetrating member 83 ispreferably reduced to a value below a desired threshold and isultimately reduced to zero. The processor 93 can reduce the speed of thepenetrating member 83 by causing a current to be sent to a 114-117 coilthat will exert an attractive braking force on the magnetic member 102in a proximal direction away from the patient's tissue or skin 133, asindicated by the arrow 190 in FIG. 13. Such a negative force reduces theforward or distally oriented speed of the penetrating member 83. Theprocessor 93 can determine which coil 114-117 to energize based upon theposition of the magnetic member 102 with respect to the coils 114-117 ofthe driver coil pack 88, as indicated by the position sensor 91.

In the next operation, the process proceeds to the withdraw phase, asrepresented by the flow diagram box numbered 177. The withdraw phasebegins with the operation represented by the flow diagram box numbered178 in FIG. 6C. Here, the processor 93 allows the penetrating member 83to settle at a position of maximum skin penetration 144, as shown inFIG. 12. In this regard, the processor 93 waits until any motion in thepenetrating member 83 (due to vibration from impact and spring energystored in the skin, etc.) has stopped by monitoring changes in positionof the penetrating member 83. The processor 93 preferably waits untilseveral milliseconds (ms), such as on the order of about 8 ms, havepassed with no changes in position of the penetrating member 83. This isan indication that movement of the penetrating member 83 has ceasedentirely. In some embodiments, the penetrating member may be allowed tosettle for about 1 to about 2000 milliseconds, specifically, about 50 toabout 200 milliseconds. For other embodiments, the settling time may beabout 1 to about 200 milliseconds.

It is at this stage of the lancing cycle that a software method can beused to measure the amount of tenting of the patient's skin 133 and thusdetermine the skin 133 characteristics such as elasticity, hydration andothers. Referring to FIGS. 37-41, a penetrating member 83 is illustratedin various phases of a lancing cycle with target tissue 133. FIG. 14shows tip 96 of penetrating member 83 making initial contact with theskin 133 at the point of initial impact.

FIG. 15 illustrates an enlarged view of the penetrating member 83 makinginitial contact with the tissue 133 shown in FIG. 14. In FIG. 16, thepenetrating member tip 96 has depressed or tented the skin 133 prior topenetration over a distance of X, as indicated by the arrow labeled X inFIG. 16. In FIG. 17, the penetrating member 83 has reached the fulllength of the cutting power stroke and is at maximum displacement. Inthis position, the penetrating member tip 96 has penetrated the tissue133 a distance of Y, as indicated by the arrow labeled Y in FIG. 16. Ascan be seen from comparing FIG. 15 with FIG. 17, the penetrating membertip 96 was displaced a total distance of X plus Y from the time initialcontact with the skin 133 was made to the time the penetrating membertip 96 reached its maximum extension as shown in FIG. 17. However, thepenetrating member tip 96 has only penetrated the skin 133 a distance Ybecause of the tenting phenomenon.

At the end of the power stroke of the penetrating member 83, asdiscussed above with regard to box 179 of FIG. 6C, the processor 93allows the penetrating member to settle for about 8 msec. It is duringthis settling time that the skin 133 rebounds or relaxes back toapproximately its original configuration prior to contact by thepenetrating member 83 as shown in FIG. 18. The penetrating member tip 96is still buried in the skin to a depth of Y, as shown in FIG. 18,however the elastic recoil of the tissue has displaced the penetratingmember rearward or retrograde to the point of inelastic tenting that isindicated by the arrows Z in FIG. 18. During the rearward displacementof the penetrating member 83 due to the elastic tenting of the tissue133, the processor reads and stores the position data generated by theposition sensor 91 and thus measures the amount of elastic tenting,which is the difference between X and Z.

Referring to FIG. 19, a tissue penetration sampling device 80 is shownwith the controllable driver 179 of FIG. 4 coupled to a sampling modulecartridge 205 and disposed within a driver housing 206. A ratchet drivemechanism 207 is secured to the driver housing 206, coupled to thesampling module cartridge 205 and configured to advance a samplingmodule belt 208 within the sampling module cartridge 205 so as to allowsequential use of each sampling module 209 in the sampling module belt208. The ratchet drive mechanism 207 has a drive wheel 211 configured toengage the sampling modules 209 of the sampling module belt 208. Thedrive wheel 211 is coupled to an actuation lever 212 that advances thedrive wheel 211 in increments of the width of a single sampling module209. A T-slot drive coupler 213 is secured to the elongated couplershaft 84.

A sampling module 209 is loaded and ready for use with the drive head 98of the penetrating member 83 of the sampling module 209 loaded in theT-slot 214 of the drive coupler 213. A sampling site 215 is disposed atthe distal end 216 of the sampling module 209 disposed about apenetrating member exit port 217. The distal end 216 of the samplingmodule 209 is exposed in a module window 218, which is an opening in acartridge cover 221 of the sampling module cartridge 205. This allowsthe distal end 216 of the sampling module 209 loaded for use to beexposed to avoid contamination of the cartridge cover 221 with bloodfrom the lancing process.

A reader module 222 is disposed over a distal portion of the samplingmodule 209 that is loaded in the drive coupler 213 for use and has twocontact brushes 224 that are configured to align and make electricalcontact with analyte detecting member contacts 225 of the samplingmodule 209 as shown in FIG. 77. With electrical contact between theanalyte detecting member contacts 225 and contact brushes 224, theprocessor 93 of the controllable driver 179 can read a signal from ananalytical region 226 of the sampling module 209 after a lancing cycleis complete and a blood sample enters the analytical region 226 of thesampling module 209. The contact brushes 224 can have any suitableconfiguration that will allow the sampling module belt 208 to passlaterally beneath the contact brushes 224 and reliably make electricalcontact with the sampling module 209 loaded in the drive coupler 213 andready for use. A spring loaded conductive ball bearing is one example ofa contact brush 224 that could be used. A resilient conductive stripshaped to press against the inside surface of the flexible polymer sheet227 along the analyte detecting member region 228 of the sampling module209 is another embodiment of a contact brush 224.

The sampling module cartridge 205 has a supply canister 229 and areceptacle canister 230. The unused sampling modules of the samplingmodule belt 208 are disposed within the supply canister 229 and thesampling modules of the sampling module belt 208 that have been used areadvanced serially after use into the receptacle canister 230.

FIG. 20 illustrates a further embodiment of sampling module cartridges.FIG. 20 shows a sampling module cartridge 202 in a carouselconfiguration with adjacent sampling modules 204 connected rigidly andwith analyte detecting members 206 from the analytical regions of thevarious sampling modules 204 disposed near an inner radius 208 of thecarousel. The sampling modules 204 of the sampling module cartridge 202are advanced through a drive coupler 213 but in a circular as opposed toa linear fashion.

FIG. 21 shows an exploded view in perspective of the cartridge 245,which has a proximal end portion 254 and a distal end portion 255. Thepenetrating member cartridge body 246 is disposed at the proximal endportion 254 of the cartridge 245 and has a plurality of penetratingmember module portions 250, such as the penetrating member moduleportion 250. Each penetrating member module portion 250 has apenetrating member channel 251 with a penetrating member 83 slidablydisposed within the penetrating member channel 251. The penetratingmember channels 251 are substantially parallel to the longitudinal axis252 of the penetrating member cartridge body 246. The penetratingmembers 83 shown have a drive head 98, shaft portion 201 and sharpenedtip 96. The drive head 98 of the penetrating members are configured tocouple to a drive coupler (not shown), such as the drive coupler 85discussed above.

The penetrating members 83 are free to slide in the respectivepenetrating member channels 251 and are nominally disposed with thesharpened tip 96 withdrawn into the penetrating member channel 251 toprotect the tip 96 and allow relative rotational motion between thepenetrating member cartridge body 246 and the sampling cartridge body247 as shown by arrow 256 and arrow 257 in FIG. 21. The radial center ofeach penetrating member channel 251 is disposed a fixed, known radialdistance from the longitudinal axis 252 of the penetrating membercartridge body 246 and a longitudinal axis 258 of the cartridge 245. Bydisposing each penetrating member channel 251 a fixed known radialdistance from the longitudinal axes 252 and 258 of the penetratingmember cartridge body 246 and cartridge 245, the penetrating memberchannels 251 can then be readily and repeatably aligned in a functionalarrangement with penetrating member channels 253 of the samplingcartridge body 247. The penetrating member cartridge body 246 rotatesabout a removable pivot shaft 259 which has a longitudinal axis 260 thatis coaxial with the longitudinal axes 252 and 250 of the penetratingmember cartridge body 246 and cartridge 245.

The sampling cartridge body 247 is disposed at the distal end portion255 of the cartridge and has a plurality of sampling module portions 248disposed radially about the longitudinal axis 249 of the samplingcartridge body 247. The longitudinal axis 249 of the sampling cartridgebody 247 is coaxial with the longitudinal axes 252, 258 and 260 of thepenetrating member cartridge body 246, cartridge 245 and pivot shaft259. The sampling cartridge body 247 may also rotate about the pivotshaft 259. In order to achieve precise relative motion between thepenetrating member cartridge body 246 and the sampling cartridge body247, one or both of the cartridge bodies 246 and 247 may be rotatableabout the pivot shaft 259, however, it is not necessary for both to berotatable about the pivot shaft 259, that is, one of the cartridgebodies 246 and 247 may be secured, permanently or removably, to thepivot shaft 259.

The sampling cartridge body 247 includes a base 261 and a cover sheet262 that covers a proximal surface 263 of the base forming a fluid tightseal. Each sampling module portion 248 of the sampling cartridge body247, such as the sampling module portion 248, has a sample reservoir 264and a penetrating member channel 253. The sample reservoir 264 has avent 965 at an outward radial end that allows the sample reservoir 264to readily fill with a fluid sample. The sample reservoir 264 is influid communication with the respective penetrating member channel 253which extends substantially parallel to the longitudinal axis 249 of thesampling cartridge body 247. The penetrating member channel 253 isdisposed at the inward radial end of the sample reservoir 264. Stillfurther description of the device of FIG. 21 may be found in commonlyassigned, copending U.S. patent application Ser. No. 10/127,395 filedApr. 19, 2002.

Referring to FIG. 22A, one embodiment of the present invention is atissue penetrating system 310 with a plurality of penetrating members312 that each have a tissue penetrating tip 314. The number ofpenetrating members 310 can vary, but numbers in the ranges of 10, 15,25, 50, 75, 100, 500 or any other number, are suitable. Each penetratingmember 312 can be a lancet, a traditional lancet with a molded body, aneedle with a lumen, a knife like element, an elongate member withoutmolded attachments, and the like, and may have a size in the range of 20mm to 10 mm in length and between 0.012-0.040 mm in diameter. It shouldbe understood of course that penetrating members of a variety ofdifferent sizes useful for lancing such as those of conventional lancetsmay be used in other embodiments. As seen in FIG. 22A, the penetratingmember may have an elongate portion with a bend near a proximal end ofthe member.

Each penetrating member 312 is coupled to a penetrating member driver316. Suitable penetrating member drivers 316 include but are not limitedto, an electric drive force member, a voice coil drive force generator,a linear voice coil device, a rotary voice coil device, and the like.Suitable drive force generators can be found in commonly assigned,copending U.S. patent application Ser. No. 10/127,395 filed Apr. 19,2002. In one embodiment, the penetrating member driver or drive forcegenerator 316 may be a single actuator used to advance the penetratingmember and to withdraw the member. The driver 316 may also be used tostop the penetrating member in the tissue site. Penetrating memberdriver 316 can be a non-spring actuator for drawing penetrating member312 in a direction back towards penetrating member driver 316. A coupler318 on penetrating member driver 316 is configured to engage at least aportion of an elongate portion of a penetrating member 312 in order todrive the penetrating member 312 along a path into and through targettissue 320, and then withdrawn from target tissue 320.

Referring now to FIG. 22B, the tips of the penetrating members 312 canbe uncovered when they are launched into a selected target tissue 320.In one embodiment, sterility enclosures 322 are provided for covering atleast the tip of each penetrating member 312. FIG. 22B shows that theenclosure may also cover the entire lancet. In one embodiment, eachsterility enclosure 322 is removed from the penetrating member 312 priorto actuation, launch, of penetrating member 312 and positioned so thatpenetrating member 312 does not contact the associated sterilityenclosure 322 during actuation. As seen in FIG. 22B, the enclosure 322may be peel away to reveal the penetrating member 312 prior to couplingof the member 312 to the drive force generator 316. In anotherembodiment, each penetrating member 312 breaches its associatedsterility enclosure 322 during launch.

Tissue penetrating system 310 can also include one or more penetratingmember sensors 324 that are coupled to penetrating members 312. Examplesof suitable penetrating member sensors 324 include but are not limitedto, a capacitive incremental encoder, an incremental encoder, an opticalencoder, an interference encoder, and the like. Each penetrating membersensor 324 is configured to provide information relative to a depth ofpenetration of a penetrating member 312 through a target tissue 320surface, including but not limited to a skin surface, and the like. Thepenetrating member sensor 324 may be positioned as shown in FIG. 22B.The penetrating member sensor 324 may also be positioned in a variety oflocation such as but not limited to being closer to the distal end ofthe penetrating member, in a position as shown in FIG. 5, or in anyother location useful for providing an indication of the position of apenetrating member 312 being driven by the force generator 316.

In various embodiments, the penetration depth of a penetrating member312 through the surface of a target tissue 320 can be, 100 to 2500microns, 500 to 750 microns, and the like. Each penetrating membersensor 324 can also provide an indication of velocity of a penetratingmember 312. Referring to FIG. 22C, a damper 326 can be coupled topenetrating member driver 316. Damper 326 prevents multiple oscillationsof penetrating member 312 in target tissue 320, particularly afterpenetrating member 312 has reached a desired depth of penetration. Thedamper 326 may be placed in a variety of positions such as but notlimited to being coupled to the penetrating member, being coupled to thecoupler 318, being coupled to a core or shaft in the drive forcegenerator 316, or at any other position useful for slowing the motion ofthe penetrating member 312.

A feedback loop 328 can also be included that is coupled to penetratingmember sensor 324. Each penetrating member 312 sensor can be coupled toa processor 330 that has control instructions for penetrating memberdriver 316. By way of illustration, and without limitation, processor330 can include a memory for storage and retrieval of a set ofpenetrating member 312 profiles utilized with penetrating member driver316. Processor 330 can also be utilized to monitor position and speed ofa penetrating member 312 as it moves in first direction 332 to andthrough the target tissue 320.

Processor 330 can adjust an application of force to a penetrating member312 in order to achieve a desired speed of a penetrating member 312.Additionally, processor 330 can also be used to adjust an application offorce applied to a penetrating member 312 when penetrating member 312contacts target tissue 320 so that penetrating member 312 penetratestarget tissue 320 within a desired range of speed. Further, processor330 can also monitor position and speed of a penetrating member 312 aspenetrating member 312 moves in first direction 332 toward the targettissue 320. Application of a launching force to penetrating member 312can be controlled based on position and speed of penetrating member 312.Processor 330 can control a withdraw force, from target tissue 320, topenetrating member 312 so that penetrating member 312 moves in seconddirection 334 away from target tissue 320.

Processor 330 can produce a signal that is indicative of a change indirection and magnitude of force exerted on penetrating member 312.Additionally, processor 330 can cause a braking force to be applied topenetrating member 312.

In one embodiment, in first direction 332 penetrating member 312 movestoward target tissue 320 at a speed that is different than a speed atwhich penetrating member 312 moves away from target tissue 320 in seconddirection 334. In one embodiment, the speed of penetrating member 312 infirst direction 332 is greater than the speed of penetrating member 312in second direction 334. The speed of penetrating member 312 in firstdirection 332 can be a variety of different ranges including but notlimited to, 0.05 to 60 m/sec, 0.1 to 20.0 m/sec, 1.0 to 10.0 m/sec, 3.0to 8.0 m/sec, and the like. Additionally, the dwell time of penetratingmember 312 in target tissue 320, below a surface of the skin or otherstructure, can be in the range of, 1 microsecond to 2 seconds, 500milliseconds to 1.5 second, 100 milliseconds to 1 second, and the like.

As seen in FIGS. 22A and 22B, tissue penetrating system 310 can includea penetrating member transport device 336 for moving each of penetratingmember 312 into a position for alignment with penetrating member driver316. Penetrating members 312 can be arranged in an array configurationby a number of different devices and structures defining support 338,including but not limited to, a belt, a flexible or non-flexible tapedevice, support channel, cog, a plurality of connectors, and the like.Support 338 can have a plurality of openings each receiving apenetrating member 312. Suitable supports 338 may also include but arenot limited to, a bandolier, drum, disc and the like. A description ofsupports 338 can be found in commonly assigned, copending U.S. patentapplication Ser. No. 10/127,395 filed Apr. 19, 2002; commonly assigned,U.S. Provisional Patent Application Ser. No. 60/437,359 filed Dec. 31,2002; and commonly assigned U.S. Provisional Patent Application Ser. No.60/437,205 filed Dec. 31, 2002. All applications listed above are fullyincorporated herein by reference for all purposes.

As illustrated in FIG. 22(a), tissue penetrating system 310 can includea single penetrating member driver 316 and a plurality of penetratingmembers 312. Penetrating member driver 316 moves each penetrating member312 along a path out of a housing that has a penetrating member exit andthen into target tissue 320, stopping in target tissue 320, and thenwithdrawing out of the target tissue 320. Support 338 couples thepenetrating members 312 to define a linear array. Support 338 is movableand configured to move each penetrating member 312 to a launch positionassociated with penetrating member driver 316. Penetrating member driver316 can be controlled to follow a predetermined velocity trajectory intoand out of target tissue 320.

Tissue penetrating system 310 can include a user interface 340configured to relay different information, including but not limited to,skin penetrating performance, a skin penetrating setting, and the like.User interface 340 can provide a user with at a variety of differentoutputs, including but not limited to, penetration depth of apenetrating member 312, velocity of a penetrating member 312, a desiredvelocity profile, a velocity of penetrating member 312 into targettissue 320, velocity of the penetrating member 312 out of target tissue320, dwell time of penetrating member 312 in target tissue 320, a targettissue relaxation parameter, and the like. User interface 340 caninclude a variety of components including but not limited to, a realtime clock 342, one or more alarms 344 to provide a user with a reminderof a next target penetrating event is needed, a user interface processor346, and the like.

User interface 340 can provide a variety of different outputs to a userincluding but not limited to, number of penetrating members 312available, number of penetrating members 312 used, actual depth ofpenetrating member 312 penetration on target tissue 320, stratum corneumthickness in the case where the target tissue 320 is the skin and anarea below the skin, force delivered on target tissue 320, energy usedby penetrating member driver 316 to drive penetrating member 312 intotarget tissue 320, dwell time of penetrating member 312, battery statusof tissue penetrating system 310, status of tissue penetrating system310, the amount of energy consumed by tissue penetrating system 310, orany component of tissue penetrating system 310, speed profile ofpenetrating member 312, information relative to contact of penetratingmember 312 with target tissue 320 before penetration by penetratingmember 312, information relative to a change of speed of penetratingmember 312 as in travels in target tissue 320, and the like.

User interface 340 can include a data interface 348 that couples tissuepenetrating system 310 to support equipment 350 with an interface, theinternet, and the like. The data interface 348 may also be coupled tothe processor 93. Suitable support equipment 350 includes but is notlimited to, a base station, home computer, central server, mainprocessing equipment for storing analyte, such as glucose, levelinformation, and the like.

Data interface 348 can be a variety of interfaces including but notlimited to, Serial RS-232, modem interface, USB, HPNA, Ethernet, opticalinterface, IRDA, RF interface, Bluetooth interface, cellular telephoneinterface, two-way pager interface, parallel port interface standard,near field magnetic coupling, RF transceiver, telephone system, and thelike.

User interface 340 be coupled to a memory 352 that stores, a targettissue parameter, target tissue 320 penetrating performance, and thelike. The memory 352 may also be connected to processor 93 and storedata from the user interface 340.

In one embodiment, memory 352 can store, the number of target tissuepenetrating events, time and date of the last selected number of targettissue penetrating events, time interval between alarm and target tissuepenetrating event, stratum corneum thickness, time of day, energyconsumed by penetrating member driver 316 to drive penetrating member312 into target tissue 320, depth of penetrating member 312 penetration,velocity of penetrating member 312, a desired velocity profile, velocityof penetrating member 312 into target tissue 320, velocity ofpenetrating member 312 out of target tissue 320, dwell time ofpenetrating member 312 in target tissue 320, a target tissue relaxationparameter, force delivered on target tissue 320 by any component oftissue penetrating device, dwell time of penetrating member 312, batterystatus of tissue penetrating system 310, tissue penetrating system 310status, consumed energy by tissue penetrating system 310 or any of itscomponents, speed profile of penetrating member 312 as it penetrates andadvances through target tissue 320, a tissue target tissue relaxationparameter, information relative to contact of penetrating member 312with target tissue 320 before penetration by penetrating member 312,information relative to a change of speed of penetrating member 312 asin travels in and through target tissue 320, information relative toconsumed analyte detecting members, and information relative to consumedpenetrating members 312.

In one embodiment, processor 330 is coupled to and receives any of adifferent type of signals from user interface 340. User interface 340can respond to a variety of different commands, including but notlimited to audio commands, and the like. User interface 340 can includea sensor for detecting audio commands. Information can be relayed to auser of tissue penetrating system 310 by way of an audio device,wireless device, and the like.

In another embodiment as seen in FIG. 23B, tissue penetrating deviceincludes a human interface 354 with at least one output. The humaninterface 354 is specific for use by humans while a user interface 340may be for any type of user, with user defined generically. Humaninterface 354 can be coupled to processor 330 and penetrating membersensor 324. Human interface 354 can be a variety of different varietiesincluding but not limited to, LED, LED digital display, LCD display,sound generator, buzzer, vibrating device, and the like.

The output of human interface 354 can be a variety of outputs includingbut not limited to, a penetration event by penetrating member 312,number of penetrating members 312 remaining, time of day, alarm,penetrating member 312 trajectory waveform profile information, force oflast penetration event, last penetration event, battery status of tissuepenetrating system 310, analyte status, time to change cassette status,jamming malfunction, tissue penetrating system 310 status, and the like.

Human interface 354 is coupled to a housing 356. Suitable housings 356include but are not limited to a, telephone, watch, PDA, electronicdevice, medical device, point of care device, decentralized diagnosticdevice and the like. An input device 358 is coupled to housing. Suitableinput devices 358 include but are not limited to, one or morepushbuttons, a touch pad independent of the display device, a touchsensitive screen on a visual display, and the like.

A data exchange device 360 can be utilized for coupling tissuepenetrating system 310 to support equipment 350 including but notlimited to, personal computer, modem, PDA, computer network, and thelike. Human interface 354 can include a real time clock 362, and one ormore alarms 364 that enable a user to set and use for reminders for thenext target tissue penetration event. Human interface 354 can be coupledto a human interface processor 366 which is distinct from processor 330.Human interface processor 366 can include a sleep mode and can runintermittently to conserve power. Human interface processor 366 includeslogic that can provide an alarm time set for a first subset of days, anda second alarm time set for a second subset of days. By way of example,and without limitation, the first subset of days can be Monday throughFriday, and the second subset of days can be Saturday and Sunday.

Human interface 354 can be coupled to a memory 368 for storing a varietyof information, including but not limited to, the number of targettissue penetrating events, time and date of the last selected number oftarget tissue penetrating events, time interval between alarm and targettissue penetrating event, stratum corneum thickness when target tissue320 is below the skin surface and underlying tissue, time of day, energyconsumed by penetrating member driver 316 to drive penetrating member312 into target tissue 320, depth of penetrating member 312 penetration,velocity of penetrating member 312, a desired velocity profile, velocityof penetrating member 312 into target tissue 320, velocity ofpenetrating member 312 out of target tissue 320, dwell time ofpenetrating member 312 in target tissue 320, a target tissue relaxationparameter, force delivered on target tissue 320, dwell time ofpenetrating member 312, battery status of tissue penetrating system 310and its components, tissue penetrating system 310 status, consumedenergy, speed profile of penetrating member 312 as it advances throughtarget tissue 320, a target tissue relaxation parameter, informationrelative to contact of a penetrating member 312 with target tissue 320before penetration by penetrating member 312, information relative to achange of speed of penetrating member 312 as in travels in target tissue320, information relative to consumed sensors, information relative toconsumed penetrating members 312.

As illustrated in FIG. 24, tissue penetrating system 310 can include apenetrating member driver 316 and a plurality of cartridges 370. Eachcartridge 370 contains a penetrating member 312. The cartridges 370 canbe coupled together in an array, which can be a flexible array. Acartridge transport device 372 moves cartridges 370 into a launchposition that operatively couples a penetrating member 312 topenetrating member driver 316. A support couples cartridges 370 todefine an array. A plurality of sterility enclosures 322 can be providedto at least cover tips of penetrating members 312. Sterility enclosure322 (shown in phantom) is removed from their associated penetratingmembers 312 prior to launch of the penetrating member 312. The enclosuremay be peeled away (not shown) in a manner similar to that as seen inFIG. 22B, with the enclosure 322 on one tape surface being peeled away.The enclosure 322 may be a blister sack, a sack tightly formed abouteach cartridge 370, or other enclosure useful for maintaining a sterileenvironment about the cartridge 370 prior to actuation or launch. Theenclosure 322 may contain the entire cartridge 370 or some portion ofthe cartridge 370 which may need to remain sterile prior to launch.During launch, enclosure or sterility barrier 322 can be breached by adevice other than penetrating member 312, or can be breached bypenetrating member 312 itself. An analyte detection member, sensor, maybe positioned to receive fluid from a wound created by the penetratingmember 312. The member may be on the cartridge 370 or may be on thedevice 80.

Referring to FIGS. 24 and 25, one embodiment of tissue penetratingsystem 310 includes cartridge transport device 372 and a plurality ofcartridges 370. Each cartridge 370 is associated with a penetratingmember 312. Cartridge transport device 372 moves each cartridge 370 to aposition to align the associated penetrating member 312 with penetratingmember driver 316 to drive penetrating member 312 along a path intotarget tissue 320. In one embodiment as seen in FIG. 25, each cartridge370 has at least one of a distal port 374 and a proximal port 376. Afirst seal 378 is positioned at distal or proximal ports. As seen inFIG. 25, the seal 378 may be placed at the distal port. First seal 378is formed of a material that is fractured by penetrating member 312before it is launched. A second seal 380 can be positioned at the otherport. It will be appreciated that only one or both of distal andproximal ports 374 and 376 can be sealed, and that each cartridge 370can include only one port 374 and 376. For ease of illustration, thepenetrating member 312 extending longitudinally through the lumen in thecartridge 370 is not shown. The seals 380 and 378 may be fracturableseals formed between the penetrating member and the cartridge 370.During actuation, the seals 378 and 380 are broken. Seal 378 may be alsobe positioned to cover the distal port or exit port 374 without beingsealed against the penetrating member (i.e. covering the port withouttouching the penetrating member). A third seal 381 may be positioned tocover an entrance to sample chamber 384. The seal 381 may be configuredto be broken when the penetrating member 312 is actuated. A stillfurther seal 381A may be placed in the lumen. The tip of a penetratingmember may be located at any position along the lumen, and may also beat or surrounded by one of the seals 378, 381, 381A, or 376.

Referring still to FIG. 25, a cover sheet 383 may be a flexible polymersheet as described in commonly assigned, copending U.S. patentapplication Ser. No. 10/127,395 filed Apr. 19, 2002. It should beunderstood of course that the sheet may be made of a variety ofmaterials useful for coupling an analyte detecting member 390. Thisallows the analyte detecting member 390 to be sterilized separately fromthe cartridge 370 and assembled together with the cartridge at a latertime. This process may be used on certain analyte detecting members 390that may be damaged if exposed to the sterilization process used on thecartridge 370. Of course, some embodiments may also have the analytedetecting member 390 coupled to the cartridge 370 during sterilization.The cover sheet 383 may also form part of the seal to maintain a sterileenvironment about portions of the penetrating member. In otherembodiments, the lumen housing penetrating member may be enclosed andnot use a sheet 383 to help form a sterile environment. In still furtherembodiments, the sheet 383 may be sized to focus on covering samplechamber 384.

As illustrated in FIG. 26, cartridge 370 has at least one port 374. Aplurality of penetrating members 312 are in cartridge 370. Althoughcartridge 370 is shown in FIG. 26 to have a linear design, the cartridge370 may also have a curved, round, circular, triangular, or otherconfiguration useful for positioning a penetrating member for use with adrive force generator. A seal 382 is associated with each penetratingmember 312 in order to maintain each penetrating member 312 in a sterileenvironment in cartridge 370 prior to launch. Prior to launch, seal 382associated with the penetrating member 312 to be launched is broken. Inone embodiment, a punch (not shown) is used to push down on the seal 382covering the port 376 of the cartridge 370. This breaks the seal 382 andalso pushes it downward, allowing the penetrating member to exit thecartridge without contacting the seal 382. The timing of the breaking ofthe seal 382 may be varied so long as the penetrating member remainssubstantially sterile when being launched towards the tissue site 320.In other embodiments, the port 376 may have a seal 383 that protrudesoutward and is broken off by the downward motion of the punch. One ormore sample chambers 384 are included in cartridge 370. In oneembodiment, each penetrating member 312 has an associated sample chamber384. In one embodiment, illustrated in FIG. 27, penetrating member 312is extendable through an opening 386 of its associated sample chamber384. In some embodiments, a seal 387 may be included in the samplechamber 384. Seals 382 and 387 may be made from a variety of materialssuch as but not limited to metallic foil, aluminum foil, paper,polymeric material, or laminates combining any of the above. The sealsmay also be made of a fracturable material. The seals may be made of amaterial that can easily be broken when a device applies a forcethereto. The seals alone or in combination with other barriers may beused to create a sterile environment about at least the tip of thepenetrating member prior to lancing or actuation.

With reference now to the embodiment of FIG. 28, each sample chamber 384may have an opening 388 for transport of a body fluid into the samplechamber 384. The size of sample chambers 384 in FIGS. 26 through 28 canvary. In various embodiments, sample chambers 384 are sized to receive,no more than 1.0 μL of the body fluid, no more than 0.75 μL of the bodyfluid, no more than 0.5 μL of the body fluid, no more than 0.25 μL ofthe body fluid, no more than 0.1 μL of the body fluid, and the like. Itwill be appreciated that sample chambers 384 can have larger or smallersizes.

An analyte detecting member 390 may associated with each sample chamber384. The analyte detecting member 390 may be designed for use with avariety of different sensing techniques as described in commonlyassigned, copending U.S. patent application Ser. No. 10/127,395 filedApr. 19, 2002. Analyte detecting member 390 can be positioned in samplechamber 384, at an exterior of sample chamber 384, or at other locationsuseful for obtaining an analyte. Analyte detecting member 390 can be ina well 392, or merely be placed on a support.

In one embodiment, analyte detecting member 390 includes chemistriesthat are utilized to measure and detect glucose, and other analytes. Inanother embodiment, analyte detecting member 390 is utilized to detectand measure the amount of different analytes in a body fluid or sample.In various embodiments, analyte detecting member 390 determines aconcentration of an analyte in a body fluid using a sample that does notexceed a volume of, 1 μL of a body fluid disposed in sample chamber 384,0.75 μL of a body fluid disposed in sample chamber 384, 0.5 μL of a bodyfluid disposed in sample chamber 384, 0.25 μL of a body fluid disposedin sample chamber 384, 0.1 μL of a body fluid disposed in sample chamber384, and the like. For example and not by way of limitation, the samplechamber 384 may be of a size larger than the volumes above, but theanalyte detecting member 390 can obtain an analyte reading using theamounts of fluid described above.

As illustrated in FIG. 29, tissue penetrating system 310 can include ahousing member 394, a penetrating member 312 positioned in housingmember 394, and analyte detecting member 390 coupled to a sample chamber384. Analyte detecting member 390 is configured to determine aconcentration of an analyte in a body fluid using with a variety ofdifferent body fluid, sample, volumes. In various embodiments, thevolume is less than 1 μL of body fluid disposed in sample chamber 384,0.75 of body fluid disposed in sample chamber 384, 0.5 of body fluiddisposed in sample chamber 384, 0.25 of body fluid disposed in samplechamber 384, 0.1 of body fluid disposed in sample chamber 384 and thelike. Each tip of a penetrating member 312 is configured to extendthrough an opening of sample chamber 384. A plurality of penetratingmembers 312 can be positioned in housing member 394. Housing member 394can be the same as cartridge 370. Cartridge 370 can have distal andproximal ports 374 and 376, respectively. Additionally, in thisembodiment, a plurality of cartridges 370 can be provided, eachassociated with a penetrating member 312.

Referring to FIG. 30, each penetrating member 312 has a packing density,or occupied volume, in cartridge 370. In various embodiments, thepacking density of each penetrating member 312 in cartridge 370 can beno more than, 5.0 cm3/penetrating member 312, 4.0 cm3/penetrating member312, 3.0 cm3/penetrating member 312, 2.0 cm3/penetrating member 312, 1.0cm3/penetrating member 312, 0.75 cm3/penetrating member 312, 0.5cm3/penetrating member 312, 0.25 cm3/penetrating member 312, 0.1cm3/penetrating member 312, and the like. In other words, the volumerequired for each penetrating member does not exceed 5.0 cm3/penetratingmember 312, 4.0 cm3/penetrating member 312, 3.0 cm3/penetrating member312, 2.0 cm3/penetrating member 312, 1.0 cm3/penetrating member 312,0.75 cm3/penetrating member 312, 0.5 cm3/penetrating member 312, 0.25cm3/penetrating member 312, 0.1 cm3/penetrating member 312, and thelike. So, as seen in FIG. 30, if the total package volume of thecartridge is defined as X and the cartridge includes Y number ofpenetrating members 312, penetrating members 312 and test area, or otherunit 395, the volume for each unit does not exceed 5.0 cm3/unit, 4.0cm3/unit, 3.0 cm3/unit, 2.0 cm3/unit, 1.0 cm3/unit, 0.75 cm3/unit, 0.5cm3/unit, 0.25 cm3/unit, 0.1 cm3/unit, and the like.

In various embodiments, each penetrating member 312 and its associatedsample chamber 384 have a combined packing density of no more than about5.0 cm3, 4.0 cm3, 3.0 cm3, 2.0 cm3, 1.0 cm3, 0.75 cm3, 0.5 cm3, 0.25cm3, 0.1 cm3, and the like.

With reference now to FIG. 31, tissue penetrating system 310 can have afirst seal 378 formed at distal port 374 and a second seal 380 formed atproximal port 376 of cartridge 370. Prior to launching of penetratingmember 312, distal seal 378 and second seal 380 maintain a distal tip ofpenetrating member 312 and sample chamber 384 in a sterile environment.Second seal 380 is breached, and penetrating member 312 is thenlaunched.

As illustrated in FIG. 32, a plurality of lumens 396 can be positionedbetween distal port 374 and proximal port 376 of cartridge 370 forslidably receiving a penetrating member 312. Sample chamber 384 isdefined by cartridge 370, has an opening 398 and is associated withpenetrating member 312. First seal 378 covers distal port 374, and asecond seal 380 covers proximal port 376.

In another embodiment as shown in FIG. 33, tissue penetrating system 310includes a plurality of cartridges 370, penetrating member driver 316,and a plurality of penetrating members 312 coupled to penetrating memberdriver 316. Each penetrating member 312 is associated with a cartridge370. A plurality of gas-tightly sealed enclosures 400 are coupled in anarray. Each enclosure 400 fully contains at least one of cartridge 370.Enclosures 400 are configured to be advanceable on cartridge transportdevice 372 that individually releases cartridges 370 from sacks orenclosures 400 and loads them individually onto penetrating memberdriver 316. The enclosures 400 may be removed by peeling back a topportion of the tape as shown in FIG. 22B.

In another embodiment, a plurality of penetrating members 312 each havea sharpened distal tip. A penetrating member driver 316 is coupled toeach penetrating member 312. A plurality of cartridges 370 are coupledin an array. Each cartridge 370 houses a penetrating member 312 and isconfigured to permit penetrating member driver 316 to engage each ofpenetrating members 312 sequentially. Each cartridge 370 has a pluralityof seals positioned to provide that the sharpened distal tips remain ina sterile environment before penetrating target tissue 320. Penetratingmembers 312 are launched without breaking a seal using the penetratingmember.

Referring now to FIG. 34, a plurality of cartridges 370 are provided,each having distal and proximal ports 374 and 376, respectively. Aplurality of penetrating members 312 are each associated with acartridge 370. Each penetrating member 312 has a sharpened distal tipand a shaft portion slidably disposed within cartridge 370. As seen inFIG. 34, the cartridges 370 may be coupled together by a connector orflexible support 403. A seal 404 is formed by a fracturable materialbetween the penetrating member 312 and each cartridge 370. Seal 404 ispositioned in at least one of distal or proximal ports 374 and 376,respectively, of cartridge 370. Cartridge transport device 372 moveseach cartridge 370 to a position 405 that aligns penetrating member 312with penetrating member driver 316 so that penetrating member 312 can bedriven along a path into target tissue 320.

In another embodiment of the present invention as seen in FIG. 35,tissue penetrating system 310 includes a housing member 406, theplurality of penetrating members 312 positioned in housing member 406,and a tissue stabilizing member 408, which can also be a pressureapplicator, stimulating member, stimulating vibratory member thatimparts motion to a tissue surface, and the like. Tissue stabilizingmember 408 can be positioned to at least partially surround an impactlocation of the penetrating member 312 on the target tissue 320 site.Tissue stabilizing member 408 can, enhance fluid flow from target tissue320, stretch a target tissue 320 surface, apply a vacuum to targettissue 320, apply a force to target tissue 320 and cause target tissue320 to press in an inward direction relative to housing member 406,apply a stimulation to target tissue 320, and the like. Tissuestabilizing member 408 can have a variety of different configurations.In one embodiment, tissue stabilizer member 408 includes a plurality ofprotrusions 410. In some further embodiments, a vacuum source 412 may beprovided to assist the creation of a low pressure environment in thetissue stabilizing member 408 or along the fluid path to a samplechamber associated with the system 310. In some embodiments, the tissuestabilizing member 408 is mounted on the cartridge 370. In otherembodiments, the member 408 may be mounted on the housing 406. Themember 408 may also be pressed against the tissue site 320 and act as apressure applicator. The member 408 may also be used against a varietyof tissue including but not limited to skin or other body tissue.

Referring now to FIGS. 36 and 37, a cartridge 370 is shown with apenetrating member 312 creating a wound W in the tissue site 320. InFIG. 36, a movable capillary member 420 is extended towards the wound Was indicated by arrow 422 to gather body fluid being expressed from thewound. The fluid may be drawn to a sample chamber 384 (not shown). InFIG. 37, the wound W is created and then the entire cartridge is movedto the tissue site 320 to gather body fluid from the wound W. In someembodiments, the cartridge 370 moves towards the wound W relative to thehousing 406.

Tissue penetrating systems 310 of FIGS. 22 through 37, can be utilizedin a variety of different applications to detect any number of differentanalytes, including but not limited to glucose. The systems 310 may beused to measure potassium, other ions, or analytes associated with theprocess of glucose monitoring. The analyte detecting member 390 mayfurther be adapted to measure other analytes found in body fluid.

In a still further embodiment, penetrating member 312 may be moved andpositioned to be in engagement with penetrating member driver 316.Penetrating member 312 is in a sterile environment, and prior to launch,the sterilizing covering, which can be a seal is removed. Tissuestabilizing member can apply a stimulation to a surface of the targettissue 320 prior to, and during penetration by penetration member.Penetrating member 312 is engaged with penetrating driving member andcontrollably pierces a target tissue 320 site. Penetrating member sensor324 is utilized to control penetration depth and velocity of penetratingmember 312. Penetrating member 312 is stopped at a desired depth below asurface of target tissue 320 in order to reduce or eliminate withoutmultiple oscillations against the surface of target tissue 320. A woundis created, causing blood to flow into sample chamber 384. In variousembodiments, no more than 1 μL of a body fluid is collected in samplechamber 384.

A number of different preferences, options, embodiment, and featureshave been given above, and following any one of these may results in anembodiment of this invention that is more presently preferred than aembodiment in which that particular preference is not followed. Thesepreferences, options, embodiment, and features may be generallyindependent, and additive; and following more than one of thesepreferences may result in a more presently preferred embodiment than onein which fewer of the preferences are followed.

While the invention has been described and illustrated with reference tocertain particular embodiments thereof, those skilled in the art willappreciate that various adaptations, changes, modifications,substitutions, deletions, or additions of procedures and protocols maybe made without departing from the spirit and scope of the invention.Any of the embodiments of the invention may be modified to include anyof the features described above or feature incorporated by referenceherein. For example, the cartridge of FIG. 26 may be adapted to includea distal portion with a tissue stabilizing member. The cartridge of FIG.26 may be adapted for use with a vacuum device. The cartridge mayinclude indexing features such as notches on the distal portion or outerradial periphery for those cartridges with a radial configuration. Thenotches will facilitate positioning, among other things, and may be usedfor movement. Other cartridges or tapes herein may be modified withnotches or tractor holes to facilitate movement. User interfaces, humaninterfaces, and other interfaces may be added to any of the embodimentsof the present invention.

With any of the above embodiments, the location of the penetratingmember drive device may be varied, relative to the penetrating membersor the cartridge. With any of the above embodiments, the penetratingmember tips may be uncovered during actuation (i.e. penetrating membersdo not pierce the penetrating member enclosure or protective foil duringlaunch). With any of the above embodiments, the penetrating members maybe a bare penetrating member during launch. With any of the aboveembodiments, the penetrating members may be bare penetrating membersprior to launch as this may allow for significantly tighter densities ofpenetrating members. In some embodiments, the penetrating members may bebent, curved, textured, shaped, or otherwise treated at a proximal endor area to facilitate handling by an actuator. The penetrating membermay be configured to have a notch or groove to facilitate coupling to agripper or coupler. The notch or groove may be formed along an elongateportion of the penetrating member. The coupler may be designed to createa frictional only type grip on the penetrating member.

With any of the above embodiments, any open cavity housing thepenetrating may be on the bottom or the top of the cartridge, with thegripper on the other side. In some embodiments, sensors may be printedon the top, bottom, or side of the cavities. The front end of thecartridge maybe in contact with a user during lancing. The same drivermay be used for advancing and retraction of the penetrating member. Thepenetrating member may have a diameters and length suitable forobtaining the blood volumes described herein. The penetrating memberdriver may also be in substantially the same plane as the cartridge. Thedriver may use a through hole or other opening to engage a proximal endof a penetrating member to actuate the penetrating member along a pathinto and out of the tissue.

Any of the features described in this application or any referencedisclosed herein may be adapted for use with any embodiment of thepresent invention. For example, the devices of the present invention mayalso be combined for use with injection penetrating members or needlesas described in commonly assigned, copending U.S. patent applicationSer. No. 10/127,395 filed Apr. 19, 2002. A sensor to detect the presenceof foil may also be included in the lancing apparatus. For example, if acavity has been used before, the foil or sterility barrier will bepunched. The sensor can detect if the cavity is fresh or not based onthe status of the barrier. It should be understood that in optionalembodiments, the sterility barrier may be designed to pierce a sterilitybarrier of thickness that does not dull a tip of the penetrating member.The lancing apparatus may also use improved drive mechanisms. Forexample, a solenoid force generator may be improved to try to increasethe amount of force the solenoid can generate for a given current. Asolenoid for use with the present invention may have five coils and inthe present embodiment the slug is roughly the size of two coils. Onechange is to increase the thickness of the outer metal shell or windingssurround the coils. By increasing the thickness, the flux will also beincreased. The slug may be split; two smaller slugs may also be used andoffset by ½ of a coil pitch. This allows more slugs to be approaching acoil where it could be accelerated. This creates more events where aslug is approaching a coil, creating a more efficient system.

In another optional alternative embodiment, a gripper in the inner endof the protective cavity may hold the penetrating member during shipmentand after use, eliminating the feature of using the foil, protectiveend, or other part to retain the used penetrating member. Some otheradvantages of the disclosed embodiments and features of additionalembodiments include: same mechanism for transferring the usedpenetrating members to a storage area; a high number of penetratingmembers such as 25, 50, 75, 100, 500, or more penetrating members may beput on a disk or cartridge; molded body about a penetrating memberbecomes unnecessary; manufacturing of multiple penetrating memberdevices is simplified through the use of cartridges; handling ispossible of bare rods metal wires, without any additional structuralfeatures, to actuate them into tissue; maintaining extreme (better than50 micron-lateral- and better than 20 micron vertical) precision inguiding; and storage system for new and used penetrating members, withindividual cavities/slots is provided. The housing of the lancing devicemay also be sized to be ergonomically pleasing. In one embodiment, thedevice has a width of about 56 mm, a length of about 105 mm and athickness of about 15 mm. Additionally, some embodiments of the presentinvention may be used with non-electrical force generators or drivemechanism. For example, the punch device and methods for releasing thepenetrating members from sterile enclosures could be adapted for usewith spring based launchers. The gripper using a frictional coupling mayalso be adapted for use with other drive technologies.

Still further optional features may be included with the presentinvention. For example, with any of the above embodiments, the locationof the penetrating member drive device may be varied, relative to thepenetrating members or the cartridge. With any of the above embodiments,the penetrating member tips may be uncovered during actuation (i.e.penetrating members do not pierce the penetrating member enclosure orprotective foil during launch). The penetrating members may be a barepenetrating member during launch. The same driver may be used foradvancing and retraction of the penetrating member. Different analytedetecting members detecting different ranges of glucose concentration,different analytes, or the like may be combined for use with eachpenetrating member. Non-potentiometric measurement techniques may alsobe used for analyte detection. For example, direct electron transfer ofglucose oxidase molecules adsorbed onto carbon nanotube powdermicroelectrode may be used to measure glucose levels. In all methods,nanoscopic wire growth can be carried out via chemical vapor deposition(CVD). In all of the embodiments of the invention, preferred nanoscopicwires may be nanotubes. Any method useful for depositing a glucoseoxidase or other analyte detection material on a nanowire or nanotubemay be used with the present invention. Expected variations ordifferences in the results are contemplated in accordance with theobjects and practices of the present invention. It is intended,therefore, that the invention be defined by the scope of the claimswhich follow and that such claims be interpreted as broadly as isreasonable.

What is claimed is:
 1. A method for injecting an agent to a tissue site,comprising: measuring an amount of elastic tenting of skin of the bodypart when a penetrating member depresses the skin in a direction inwardbelow a surface of the skin to determine elasticity of the skin; storingin a processor the amount of elastic tenting of the skin; selecting adriver profile from a set of alternative driver profiles stored in theprocessor that includes elastic tenting of the skin and a depth settingusing stored tenting information in the processor, which is dependent ona value of the measured amount of elastic tenting and influences theinjection of the agent; settling at the depth setting for a certainperiod of dwell time before starting to withdraw from the withdrawalsite; injecting an agent; wherein the dwell time is related to theamount of elastic tenting of the skin depressed by the penetratingmember trying to puncture the surface of the skin and variance in skindeformation.
 2. The method of claim 1, wherein selecting a settingincludes determining at least one of the penetrating member position andacceleration.
 3. A method for injecting an agent to a tissue site,comprising: measuring an amount of elastic tenting of skin of the bodypart when a penetrating member depresses the skin during a number ofagent injections, the elastic skin tenting being in a direction inwardbelow a surface of the skin; storing in a processor the amount ofelastic tenting of the skin; selecting a driver profile from a set ofalternative driver profiles stored in the processor that includeselastic tenting of the skin; using the penetrating member to create apenetration of the skin to the tissue site in response to the driverprofile that is selected from the processor; using the driver profileinformation that is selected to deliver the agent at the tissue site. 4.The method of claim 3, wherein at least one of the following settings isselected from the processor: blocking or releasing of a penetratingmember; setting a puncture or brake depth of a penetrating memberselected for creating the opening in the body; setting a geometric shapeof a press-on area of a system for injecting the agent; displaying texton a display device; and displaying or setting evaluation parameterswhich are used by a system for analyzing body fluid.
 5. The method ofclaim 3, further comprising: providing an audio output of relating tothe injection.
 6. The method of claim 3, wherein a depth of penetrationof a penetrating member is 100 to 2500 microns.
 7. The method of claim3, wherein a depth of penetration of a penetrating member is 500 to 750microns.
 8. The method of claim 3, further comprising: using a feedbackloop coupled to a processor.
 9. The method of claim 3, wherein in afirst direction a penetrating member moves toward a target tissue at aspeed that is different than a speed at which the penetrating membermoves away from the target tissue.
 10. The method of claim 3, wherein ina first direction a penetrating member moves toward a target tissue at aspeed that is greater than a speed at which the penetrating member movesaway from the target tissue.
 11. The method of claim 9, wherein a speedof a penetrating member in the first direction is the range of 0.05 to60 m/sec.
 12. The method of claim 9, wherein a speed of a penetratingmember in the first direction is the range of 0.1 to 20.0 m/sec.
 13. Themethod of claim 9, wherein a speed of a penetrating member in the firstdirection is the range of 1.0 to 10.0 m/sec.
 14. The method of claim 9,wherein a speed of a penetrating member in the first direction is therange of 3.0 to 8.0 m/sec.
 15. The method of claim 3, wherein a dwelltime of a penetrating member in a target tissue below a skin surface isin the range of 1 microsecond to 2 seconds.
 16. The method of claim 3,wherein a dwell time of a penetrating member in a target tissue below askin surface is in the range of 500 milliseconds to 1.5 second.
 17. Themethod of claim 3, wherein a dwell time of a penetrating member in atarget tissue below a skin, surface is in the range of 100 millisecondsto 1 second.